Association between inflammatory mediators and response to inhaled nitric oxide in a model of endotoxin-induced lung injury.
BACKGROUND
Inhaled nitric oxide (INO) allows selective pulmonary vasodilation in acute respiratory distress syndrome and improves PaO2 by redistribution of pulmonary blood flow towards better ventilated parenchyma. One-third of patients are nonresponders to INO, however, and it is difficult to predict who will respond. The aim of the present study was to identify, within a panel of inflammatory mediators released during endotoxin-induced lung injury, specific mediators that are associated with a PaO2 response to INO.


METHODS
After animal ethics committee approval, pigs were anesthetized and exposed to 2 hours of endotoxin infusion. Levels of cytokines, prostanoid, leucotriene and endothelin-1 (ET-1) were sampled prior to endotoxin exposure and hourly thereafter. All animals were exposed to 40 ppm INO: 28 animals were exposed at either 4 hours or 6 hours and a subgroup of nine animals was exposed both at 4 hours and 6 hours after onset of endotoxin infusion.


RESULTS
Based on the response to INO, the animals were retrospectively placed into a responder group (increase in PaO2 > or = 20%) or a nonresponder group. All mediators increased with endotoxin infusion although no significant differences were seen between responders and nonresponders. There was a mean difference in ET-1, however, with lower levels in the nonresponder group than in the responder group, 0.1 pg/ml versus 3.0 pg/ml. Moreover, five animals in the group exposed twice to INO switched from responder to nonresponder and had decreased ET-1 levels (3.0 (2.5 to 7.5) pg/ml versus 0.1 (0.1 to 2.1) pg/ml, P < 0.05). The pulmonary artery pressure and ET-1 level were higher in future responders to INO.


CONCLUSIONS
ET-1 may therefore be involved in mediating the response to INO.
Trachsel
Sebastien
S
Department of Medical Sciences, Clinical Physiology, Uppsala University, S-75185 Uppsala, Sweden.
Deby-Dupont
Ginette
G
Maurenbrecher
Edwige
E
Nys
Monique
M
Lamy
Maurice
M
Hedenstierna
Göran
G
D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D018836:Inflammation Mediators / Q000097:blood*; D055370:Lung Injury / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000009:adverse effects; D034421:Sus scrofa
D004731:Endotoxins; D018836:Inflammation Mediators; D009569:Nitric Oxide